Patients with epilepsy experience a variety of endocrine-related problems, of which the most widely reported is the effect on sexual function. A precise etiology for the effect on sexual function has not been established. Both a direct effect on steroid hormone levels and an indirect CNS effect have been suggested. The specific aims of this proposal are based on the hypothesis that antiepileptic drugs (AEDs) cause endocrine-related effects by interacting with adrenal and gonadal enzymes involved in steroid synthesis and/or hepatic enzymes involved in steroid degradation. Specifically, we evaluated the effects of the AED known as valproic acid. Adrenal glands, liver, testicles and ovaries from Macaca nemestrina were obtained from the tissue program at the Washington RPRC. In the initial studies we determined the optimal culture conditions for adrenal glands, testes and ovaries. Valproic acid had a direct effect on cortisol production in adrenal cells and estradiol production in ovarian and testicular cells, suggesting that the endocrine side effects of valproic acid are caused by direct interaction with the enzymes involved in steroid synthesis and/or degradation.